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Increased Efficiency of Salinomycin Analogs in a Breast Cancer Cell Line

Labačevskaja, Veronika (2013) MOBT15 20122
Degree Projects in Molecular Biology
Abstract
Popular science summary:

A growing body of evidence shows that tumors consist of rare cancer stem cells (CSCs), precursor cells and differentiated tumor cells. CSCs are today thought to be the main culprit in the tumor origin, progression, recurrence and resistance to therapy. The origin of CSC is enigmatic; however, it has been suggested that CSCs can arise from any type of cells and the underlying cause is always genetic mutation. CSCs and normal stem cells share several fundamental properties, namely asymmetric division, self-renewal and multipotent differentiation. Also, CSCs express high level of specific drug transporters that ensures drug efflux and makes CSCs highly resistant to current therapies. In the present study I have... (More)
Popular science summary:

A growing body of evidence shows that tumors consist of rare cancer stem cells (CSCs), precursor cells and differentiated tumor cells. CSCs are today thought to be the main culprit in the tumor origin, progression, recurrence and resistance to therapy. The origin of CSC is enigmatic; however, it has been suggested that CSCs can arise from any type of cells and the underlying cause is always genetic mutation. CSCs and normal stem cells share several fundamental properties, namely asymmetric division, self-renewal and multipotent differentiation. Also, CSCs express high level of specific drug transporters that ensures drug efflux and makes CSCs highly resistant to current therapies. In the present study I have investigated the effect of a known CSC inhibiting compound and two newly synthesized analogs against breast CSCs.

The SK-BR-3 breast cancer cell line was used for the studies. Initially, dose response experiments were performed to deduce concentrations used for further studies. Two doses were chosen to investigate the effect on cell proliferation and cell cycle distribution. The two analogs were more efficient in inhibiting proliferation than the parental compound. The cells were blocked in the G1 phase of the cell cycle presumably as a result of the increase in the cell cycle inhibitor p27 as well as decreased cyclin D and E levels investigated by Western blot.

The colony forming efficiency of the SK-BR-3 cells was evaluated by seeding cells at cloning density in soft agar. It has been shown, that this culture environment only can support CSC growth and colony formation. Treatment with the parental compound and analogs reduced colony number, however, the analogs were significantly better the parental compound. Also, as illustrated in Figure 1, treatment with analogs resulted in smaller colonies compared to control and treatment with the parental compound.

In conclusion, this study shows that breast cancer cells as well as putative breast CSCs are more sensitive to the two newly synthesized analogs than to the parental compound.



Advisor: Prof. Stina Oredsson
Master´s Degree Project 60 credits in Cell and Molecular Biology 2013
Department of Biology, Lund University (Less)
Please use this url to cite or link to this publication:
author
Labačevskaja, Veronika
supervisor
organization
course
MOBT15 20122
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
3814078
date added to LUP
2013-06-17 09:17:40
date last changed
2013-06-17 09:17:40
@misc{3814078,
  abstract     = {Popular science summary:

A growing body of evidence shows that tumors consist of rare cancer stem cells (CSCs), precursor cells and differentiated tumor cells. CSCs are today thought to be the main culprit in the tumor origin, progression, recurrence and resistance to therapy. The origin of CSC is enigmatic; however, it has been suggested that CSCs can arise from any type of cells and the underlying cause is always genetic mutation. CSCs and normal stem cells share several fundamental properties, namely asymmetric division, self-renewal and multipotent differentiation. Also, CSCs express high level of specific drug transporters that ensures drug efflux and makes CSCs highly resistant to current therapies. In the present study I have investigated the effect of a known CSC inhibiting compound and two newly synthesized analogs against breast CSCs. 

The SK-BR-3 breast cancer cell line was used for the studies. Initially, dose response experiments were performed to deduce concentrations used for further studies. Two doses were chosen to investigate the effect on cell proliferation and cell cycle distribution. The two analogs were more efficient in inhibiting proliferation than the parental compound. The cells were blocked in the G1 phase of the cell cycle presumably as a result of the increase in the cell cycle inhibitor p27 as well as decreased cyclin D and E levels investigated by Western blot. 

The colony forming efficiency of the SK-BR-3 cells was evaluated by seeding cells at cloning density in soft agar. It has been shown, that this culture environment only can support CSC growth and colony formation. Treatment with the parental compound and analogs reduced colony number, however, the analogs were significantly better the parental compound. Also, as illustrated in Figure 1, treatment with analogs resulted in smaller colonies compared to control and treatment with the parental compound. 

In conclusion, this study shows that breast cancer cells as well as putative breast CSCs are more sensitive to the two newly synthesized analogs than to the parental compound. 



Advisor: Prof. Stina Oredsson
Master´s Degree Project 60 credits in Cell and Molecular Biology 2013
Department of Biology, Lund University},
  author       = {Labačevskaja, Veronika},
  language     = {eng},
  note         = {Student Paper},
  title        = {Increased Efficiency of Salinomycin Analogs in a Breast Cancer Cell Line},
  year         = {2013},
}